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The National Institutes of Health (NIH) announced Thursday a new program dubbed the Common Fund’s Somatic Mosaicism Across Human Tissues (SMaHT) Network, a five-year $140 million effort to better understand the level of genetic variation present in cells throughout the human body. The SMaHT Network will be managed collaboratively among a number of different NIH offices including the NIH Common Fund, the NHGRI, the National Institute on Drug Abuse, the National Institute of Environmental Health Sciences, the National Institute of Mental Health, and NINDS.

Somatic mosaicism arises when some of our cells when some of the cells in a human body accumulate DNA changes over time. These changes can alter how cells function and can influence the development of disease, aging, and other physiological changes over a person’s life.

“As somatic mosaicism can occur in any cell type in our bodies, it could have wide-reaching impacts on our health. The breadth of mosaicism’s reach makes it unwieldy for just one NIH Institute or Center to address alone,” said Robert Eisinger, PhD, acting director of NIH’s Division of Program Coordination, Planning, and Strategic Initiatives. “This makes the study of somatic mosaicism a good fit for an NIH Common Fund program, since it was established to catalyze research within the broad mission of NIH.”

NIH has issued 22 awards to establish the SMaHT Network, areas hat have received investment include:

  • Procurement center to collect a common set of 10 to 15 tissues from 150 post-mortem human donors
  • Genome characterization centers to identify and describe the diversity of somatic genetic variation in the tissues
  • Data analysis center to create a catalog of this somatic genetic variation and a data workbench to visualize and analyze the variation which will integrate with existing genetic tools and databases
  • Tool development projects to create new DNA sequencing and analysis technologies that address challenges in detecting rare genetic changes that occur in regions of repetitive DNA sequences and in small populations of cells
  • Organizational center to coordinate the Network’s activities and distribute Network resources to the research community.

To ensure diverse representation, the SMaHT Network will sample tissues from a pool of human donors that include diverse ancestries and different life stages. The common set of tissues to be collected from each donor will represent different tissue types throughout the body and will likely include samples derived from the brain, blood, skin, muscle, colon, spleen, uterus, vas deferens, ovaries, and testes.

The SMaHT Network builds on other landmark projects, like the Human Genome Project and the Common Fund’s Epigenomics Program, and will examine parts of our DNA that have been difficult to sequence using current DNA sequencing tools. For instance, cell- and tissue-specific genetic changes often occur in rare populations of cells and can exist in repetitive DNA regions that are difficult to characterize. In addition, the extent of somatic mosaicism in humans may be influenced by the relative timing of the genetic change. The SMaHT Network will work to develop new technologies that have an improved ability to detect somatic mosaicism in different cell types and tissues and across different human life stages.

Walter Koroshetz, MD, the director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS), noted that “advancing technologies to identify somatic mutations, including those due to movement of transposable elements or so called ‘jumping genes,’ over time, will lead to a new understanding of age-related disorders.”

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